Combination of SIR-Spheres and Sorafenib confers survival benefit for patients with inoperable HCC

A unique combination of liver targeted radioactive microspheres (SIR-Spheres) and a standard-of-care systemic agent (Sorafenib) appears to confer a survival benefit for patients with inoperable primary hepatocellular cancer (HCC) including those with disease that has spread outside the liver, according to the results of a prospective clinical study presented today at the 46^th American Society of Clinical Oncology (ASCO) conference. The multi-center Phase II study was conducted by the Asia Pacific Hepatocellular Carcinoma Trials Group (AHCC) headed by Professor Pierce Chow, Senior Consultant, Singapore General Hospital and Visiting Senior Consultant, National Cancer Center Singapore.

“The results of this study demonstrate that the combination of radioactive microspheres and a systemic agent is a promising therapy for patients with primary liver cancer, including those in whom the cancer has spread outside the liver”

The Phase I/II trial was designed to evaluate tumor response and overall survival in patients presenting with inoperable HCC in an investigator-initiated prospective multi-center study which previously reported the safety and tolerability of the combined therapies. Patients with inoperable HCC with or without extra-hepatic spread and/or major vascular involvement were eligible to receive treatment. Patients received SIR-Spheres radioactive microspheres (Sirtex Medical Limited, Lane Cove, Australia) targeted to the liver followed by sorafenib therapy (Bayer-Schering Pharmaceuticals, Leverkusen, Germany) 11-14 days later. The patients were followed monthly with clinic visits and an assessment of tumor was conducted by CT scan every three months.

The results of the 35-patient study conducted in four countries in the Asia-Pacific region (Singapore, South Korea, Myanmar and Malaysia) revealed a median overall survival of 11.75 months. Overall survival for patients with major vascular invasion (MVI) and/or extra-hepatic spread (EHS) vs. those without MVI/EHS was 8.75 months and 18.25 months, respectively. This compared very favorably with an overall survival of 5.6 months and 14.3 months respectively in patients on sorafenib alone in a landmark Asia-Pacific study. The overall tumor response rate was 35.5%, with 12% complete response (CR), 23.5% partial response (PR), 44% stable disease (SD) and 21% progressive disease (PD) with an overall disease control rate of 79.5%. Three patients (9%) who initially presented with unresectable disease had a sufficient reduction in tumor size to permit potentially curative therapy, including 1 who had liver transplantation and 2 who received radio-frequency ablation.

"The results of this study demonstrate that the combination of radioactive microspheres and a systemic agent is a promising therapy for patients with primary liver cancer, including those in whom the cancer has spread outside the liver," said Professor Chow. "It is particularly noteworthy that the response of tumors and median overall survival of 11.75 months in these difficult to treat patients are very favorable when compared to the therapeutic effect of either agent alone. Patients in the advanced stages of disease, particularly those with major vascular invasion in the liver and spread of disease outside the liver are not candidates for potentially curative therapies such as surgical resection, transplantation or radio-frequency ablation. Thus these patients present with a very poor prognosis with the expectation of limited survival. The combination of SIR-Spheres and sorafenib confers a clear survival benefit in this patient population who has limited treatment options available. Based on the results of this study, we are very optimistic that the survival benefit observed for this unique combination of the two agents will be confirmed by Phase III studies."

Each year, approximately 1 million individuals are diagnosed with HCC worldwide. Approximately 85% of these are not eligible for potentially curative therapies such as resection, liver transplantation or radio-frequency ablation due to the advanced stage of their disease.